A mutation in the α tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy

Abstract

Nemaline myopathies are diseases characterized by the presence in muscle fibres of pathognomonic rod bodies. These are composed largely of α–actinin and actin. We have identified a missense mutation in the α–tropomyosin gene, TPM3, which segregates completely with the disease in a family whose autosomal dominant nemaline myopathy we had previously localized to chromosome 1p13–q25. The mutation substitutes an arginine residue for a highly conserved methionine in a putative actin–binding site near the N terminus of the α–tropomyosin. The mutation may strengthen tropomyosin – actin binding, leading to rod body formation, by adding a further basic residue to the postulated actin–binding motif. © 1991 Nature Publishing Group.